Stimulation of cyclo-oxygenase by lidocaine, a pro-lipoperoxidant

Lidocaine, which was recently demonstrated to be a good pro-lipoperoxidant, was tested on in vitro PGs biosynthesis, and on arachidonate-induced arterial hypotension, in the rabbit. In the in vitro experiments, lidocaine alone was a poor stimulant of cyclo-oxygenase, but it enhanced significantly the cyclo-oxygenase activation of uric acid. In the rabbit, lidocaine lowered the i.v. arachidonate dose necessary to obtain a significant drop of blood pressure.     

Circadian rhythm of apical Na-channels and Na-transport in rabbit distal colon

In vivo and in vitro studies showed that electrogenic sodium transport in rabbit distal colon is modulated by aldosterone. It varies in a circadian rhythm; the external synchronizer is the light-dark cycle. The site of regulation was found to be in the apical membrane of colonic epithelial cells, in which the number of conducting sodium-channels is increased by aldosterone.     

Circadian rhythm of apical Na-channels and Na-transport in rabbit distal colon

Summary In vivo and in vitro studies showed that electrogenic sodium transport in rabbit distal colon is modulated by aldosterone. It varies in a circadian rhythm; the external synchronizer is the light-dark cycle. The site of regulation was found to be in the apical membrane of colonic epithelial cells, in which the number of conducting sodium-channels is increased by aldosterone.     

Is prostacyclin subserving a vasodilator effect of methoxamine involving alpha adrenoreceptors?

The influence of methoxamine on the contractile tension of isolated rat abdominal aorta, and on its capacity to produce a platelet antiaggregating substance, were explored. Methoxamine stimulated platelet antiaggregation and diminished arterial tone. The last action was blocked by phentolamine as well as by inhibitors of cyclo-oxygenase and prostacyclinsynthetase.     

Combined effect of veratridine and sodium aspartate on the rabbit retinas in vitro

Summary Combined effect of veratridine and sodium aspartate on rabbit retinas in vitro was studied. Observations suggested that mode of action of veratridine on the PII and PIII components of ERGs was modified by the presence of sodium aspartate in perfusate.     

Effect of hormones on adenyl cyclase activity of rabbit mammary gland in vitro

Ovarian hormones namely beta-estradiol and progesterone were observed to stimulate the activity of adenyl cyclase of the mammary gland from pregnant rabbit in vitro, unlike the lactating tissue where it was inhibited. On the other hand, non-ovarian hormones like hydrocortisone, prolactin and insulin did not have a similar effect on this enzyme.     

Immunological and morphological consequences of vasectomy in the rabbit.

Cell-mediated immunity to spermatozoa was detected in vitro 6--18 months after vasectomy in the rabbit. The autoimmunity was accompanied by aspermatogenic orchitis in the testes and epididymides.     

Platelet aggregation and stimulation of leucocyte procoagulant activity by rickettsial lipopolysaccharides in rabbits and in man

Summary The effects in vitro of 4 purified lipopolysaccharide (LPS) preparations from Rickettsiae on platelets and leucocytes were studied in rabbits and in man. All LPS induced aggregation in rabbit platelet-rich plasma but to differing degrees. This activity was abolished by inactivation of complement. None of the preparations induced aggregation of human platelets. Both rabbit and human leucocytes, when incubated with each of the rickettsial LPS preparations, generated a potent procoagulant activity (tissue factor). These findings add further support to the concept that rickettsial LPS behave as typical LPS from gram-negative bacteria and may be relevant to the understanding of the mechanism(s) responsible for triggering intravascular coagulation in rickettsial diseases.     

Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities.

Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1--0.5 mM, but inhibited by higher concentrations.     

Chemotaxis of rabbit macrophages in vitro: Inhibition by drugs

Summary Chemotaxis of rabbit macrophages was inhibited in vitro by phenylbutazone and sodium salicylate, but not by other antiinflammatory agents. Other inhibitory compounds were colchicine, vincristine, PHA, Con A, iodoacetic acid, cytochalasin B, and EDTA. Some of these in vitro results contrast apparently with in vivo effects.     

In situ aging of auricular chondrocytes is not due to the exhaustion of their replicative potential

Summary Multiplication of chondrocytes during growth of rabbit auricular cartilage was estimated on the basis of total DNA determination and compared with the population doubling level reached by these chondrocytes in vitro. The results indicate that the in situ aging of auricular chondrocytes is caused by factors other than the intrinsic depletion of their growth potential.     

Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro

Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analog, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.     

Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities

Summary Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1–0.5 mM, but inhibited by higher concentrations.Acknowledgment. Supported by a grant from the Orion and Medica Scientific Foundation, Finland.     

Highly efficient cell-mediated gene transfer using non-viral vectors and FuGene6: in vitro and in vivo studies

The present study was undertaken to develop an efficient non-viral gene delivery system for cardiovascular gene therapy. We investigated transfection efficiency and toxic properties of the new transfection reagent, FuGene6, and compared it with two other transfection reagents, Tfx-50 and LipoTaxi. For in vivo experiments, the plasmid was delivered intramuscularly via transplantation of fibroblasts transfected with plasmid and FuGene6. Conditions for efficient gene delivery were initially studied in vitro. Human and rabbit fibroblasts were isolated from skin, cultured and transfected with phVEGF165 or pCMVbeta gal plasmids, coding for vascular endothelial growth factor (VEGF) or beta-galactosidase, respectively. The effect of the DNA amount and the DNA:transfection reagent ratio on plasmid uptake were studied. Of the transfection reagents tested, only FuGene6 provided high-efficiency and dose-dependent plasmid transfer both for cell-localised (beta-galactosidase) and secreted (VEGF) gene products. When analysed with an MTT assay, FuGene6 showed no toxicity at low doses. Optimised conditions were applied for in vivo reporter gene delivery. Rabbits were injected intramuscularly with ex vivo-transfected fibroblasts. As in in vitro studies, ex vivo-transfected fibroblasts showed highly efficient gene expression in vivo. Tissue sections were analysed with macrophage-specific immunostaining. No signs of inflammation were seen in the region of fibroblast injection. This study demonstrates that FuGene6 is a highly efficient transfection reagent that may be useful for in vitro non-viral transfection of primary human and rabbit fibroblasts and for in vivo therapeutic non-viral gene delivery.     

Immunological and morphological consequences of vasectomy in the rabbit

Summary Cell-mediated immunity to spermatozoa was detected in vitro 6–18 months after vasectomy in the rabbit. The autoimmunity was accompanied by aspermatogenic orchitis in the testes and epididymides.Acknowledgments. We acknowledge the financial support of the Australian Research Grants Committee and the Australian and Kenyan Governments for support through the Australian Development Assistance Bureau.     

Viability of rabbit bone marrow after cryopreservation (in vitro and in vivo)

Summary A technique for preservation of rabbit bone marrow is described, which preserves viability of stem cells in all 22 animals as tested by autologous bone marrow transplantation and in vitro growth. Erythroid precursors survived better than myeloid precursors as observed by in vitro and in vivo recovery.Supported by the Swiss Science Fondation 3.846.0.79.     

Effect of hormones on adenyl cyclase activity of rabbit mammary gland in vitro

Summary Ovarian hormones namely-estradiol and progesterone were observed to stimulate the activity of adenyl cyclase of the mammary gland from pregnant rabbit in vitro, unlike the lactating tissue where it was inhibited. On the other hand, non-ovarian hormones like hydrocortisone, prolactin and insulin did not have a similar effect on this enzyme.Acknowledgement. We are indebted to Dr D. Sundaresan, for his kind encouragement in this study.     

Effects of dobutamine on cyclic AMP accumulation induced by the stimulation of dopamine receptors in rabbit retina in vitro

Summary Intact rabbit retinae were used for testing in vitro the potential activation of dopamine receptors by a new cardioactive sympathetic amine dobutamine. It was found that despite the structure relationship of dobutamine with other dopamine-analogs, the pharmacological action of this compound is not comparable to that of apomorphine, N-methyl-dopamine and/or ADTN.Acknowledgments. Supported by SNSF grant No. 3.327.078. The authors express their gratitude to Miss G. Allenbach for her excellent technical assistance and to Mr F. Pillonel for drawing the graphs.     

Ancient DNA from Bronze Age bones of European rabbit (Oryctolagus cuniculus)

The European rabbit (Oryctolagus cuniculus) is now widely distributed throughout the world as a result of transportation by man. The original populations, however, were confined to southern France and Spain. In order to investigate the role of human intervention in determining the genetic diversity of rabbit populations, we are studying the origin of rabbits introduced onto a small Mediterranean island (Zembra) near Tunis over 1400 years ago, by examining ancient DNA extracted from rabbit bones found both on Zembra and on the European mainland. Ancient DNA was successfully extracted from rabbit bones found at two archaeological sites dated to at least the Early Bronze Age (more than 3500 years ago) in south-central France, and compared to that found in modern mainland and island populations using a small variable region of the cytochromeb gene. The results confirm that the Zembra Island population is descended from that present over 1400 years ago. The technical aspects of DNA extraction from bones and the implications of this type of research for determining the origin of introduced rabbit populations are discussed.